Fig. 23.6 ). Zone 1 represents the lung apex, where Pa is so low that it can be exceeded by PA. The capillaries collapse because of the greater external PA, and blood flow ceases. Under normal conditions, this zone does not exist; however, this state could be reached during positive-pressure mechanical ventilation or if Pa decreases sufficiently (such as might occur with a marked decrease in blood volume). In zone 2, or the upper third of the lung, Pa is greater than PA, which is in turn is greater than Pv. Because PA is greater than Pv, the greater external PA partially collapses the capillaries and causes a “damming” effect. This phenomenon is often referred to as the waterfall effect. In zone 3, Pa is greater than Pv, which is greater than PA, and blood flows in this area in accordance with the pressure gradients. Thus, pulmonary blood flow is greater in the base of the lung because the increased trans-mural pressure distends the vessels and lowers the resistance.
Active Regulation of Blood Flow
Blood flow in the lung is regulated primarily by the passive mechanisms described previously. There are, however, several active mechanisms that regulate blood flow. Although the smooth muscle around pulmonary vessels is much thinner than that around systemic vessels, it is sufficient to affect vessel caliber and thus PVR. Oxygen levels have a major effect on blood flow. Hypoxic vasoconstriction occurs in arterioles in response to decreased PAO2. The response is local, and the result is the shifting of blood flow from
CHAPTER 23 Ventilation, Perfusion, and Ventilation/Perfusion Relationships
AT THE CELLULAR LEVEL • BOX 23.1 Factors and Hormones That Regulate Pulmonary Blood Flow hypoxic areas to well-perfused areas in an effort to enhance gas exchange. Isolated, local hypoxia does not alter PVR; approximately 20% of the vessels must be hypoxic before a change in PVR can be measured. Low inspired O2 levels as a result of high altitude have a greater effect on PVR because all vessels are affected. High levels of inspired O2 can dilate pulmonary vessels and decrease PVR. Other factors and some hormones (
Box 23.1 ) can also influence vessel caliber, but their effects are usually local, brief, and important only in pathological conditions. Pulmonary capillaries lack smooth muscle and are thus not affected by these mechanisms. In some individuals, as a consequence of chronic hypoxia or collagen vascular disease, or for no apparent reason, pulmonary artery vascular resistance and subsequently pulmonary artery pressures rise (pulmonary artery hypertension).
Both ventilation (V̇ ) and lung perfusion (Q̇ ) are essential components of normal gas exchange, but a normal relationship between the two components is insufficient to ensure normal gas exchange. The ventilation/perfusion ratio (also referred to as the V̇ /Q̇ ratio) is defined as the ratio of ventilation to blood flow. This ratio can be defined for a single alveolus, for a group of alveoli, or for the entire lung. At the level of a single alveolus, the ratio is defined as alveolar ventilation per minute (V̇ A) divided by capillary flow (Q̇ c). At the level of the lung, the ratio is defined as total alveolar ventilation divided by cardiac output. In normal lungs, alveolar ventilation is approximately 4.0 L/min, whereas pulmonary blood flow is approximately 5.0 L/min. Thus
Endothelin-1 is an amino acid peptide that is produced by the vascular endothelium. Endothelin regulates the tone of pulmonary arteries, and increased expression of endothelin-1 has been found in individuals with pulmonary artery hypertension. Endothelin-1 also decreases endothelial expression of nitric oxide synthase, which reduces levels of nitric oxide, an endothelial vasodilator. Endothelin-1 antagonists (e.g., bosentan, sitaxentan) have been produced and are important drugs in the treatment of pulmonary arterial hypertension.